Previous studies have shown that small intestinal mucosal function is altered in pancreatic disease and diabetes. The objective of this proposal is to further investigate the interactions of exocrine and endocrine pancreas (induction of diabetes) with the digestive and absorptive function of the brush-border. The following related groups of studies will be performed: 1) Studies will be performed to examine the effect of pancreatic secretion and proteolytic enzymes in particular, on brush border and cytoplasmic enzymes; the effect of pancreatic enzyme replacement will be also studied. An experimental model, CBA/J mice with exocrine pancreatic insufficiency will be used. 2) Intestinal perfusion studies will be performed in patients with chronic pancreatitis to determine digestion and absorption of sugars, amino acids and peptides. Relative rates of hydrolysis and absorption will be compared with those in the control group. 3) Studies will be performed to examine the effect of intestinal mucosal function on exocrine pancreas both in the experimental animal with mucosal injury (radiation enteritis), as well as in patients with celiac sprue. 4) Segmental intestinal perfusion studies with different peptides will be performed in diabetic rats to examine peptide digestion and absoption, since intestinal peptidases are increased in experimental diabetes and endocrine as well as exocrine pancreas affects the brush border. Because of the variation in the subcellular localization of peptidases, different peptide substrates will be used to compare digestion and absorption rates between diabetic and control animals. These studies will provide information concerning: 1) the role of luminal (pancreatic secretion) and hormonal factors (insulin deficiency) in the control of brush-border enzymes, and 2) the effect of intestinal mucosal function on exocrine pancreas both in the experimental setting and in disease.